The primary cause of poor outcome following allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) is disease recurrence. Detection of increasing minimal residual disease (MRD) following HCT may permit early intervention to prevent clinical relapse; however, MRD quantification remains an uncommon diagnostic test because of logistical and financial barriers to...

PURPOSE The Vδ1+ subset of γδ T lymphocytes is a promising candidate for cancer immunotherapy, but the lack of suitable expansion/differentiation methods has precluded therapeutic application. We set out to develop and test (preclinically) a Vδ1+ T-cell-based protocol that is good manufacturing practice compatible and devoid of feeder cells for prompt clinical translation. EXPERIMENTAL DESIGN...

Ceramide is a sphingolipid metabolite that induces cancer cell death. When C6-ceramide is encapsulated in a nanoliposome bilayer formulation, cell death is selectively induced in tumor models. However, the mechanism underlying this selectivity is unknown. As most tumors exhibit a preferential switch to glycolysis, as described in the "Warburg effect", we hypothesize that ceramide nanoliposomes ...

Pyrrolo-1,5-benzoxazepine-15 (PBOX-15) is a novel microtubule depolymerization agent that induces cell cycle arrest and subsequent apoptosis in a number of cancer cell lines. Chronic lymphocytic leukemia (CLL) is characterized by clonal expansion of predominately nonproliferating mature B cells. Here, we present data suggesting PBOX-15 is a potential therapeutic agent for CLL. We show activity ...

Treatment-induced loss of targeted cell surface antigens through trogocytosis or internalization reduces efficacy of monoclonal antibody (mAb) therapy of cancer. However, cells that escape therapy mediated by complementfixing mAbs carry covalently deposited complement activation fragments on their cell surfaces, in particular C3d. We hypothesized that cell-associated C3d constitutes a neoantige...

BACKGROUND Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication study in the Prostate, Lung, Colorectal, and Ovarian (PLCO) study and pooled with published ATBC (A...

The development and the propagation of chronic lymphocytic leukemia (CLL) has been linked to signaling via the B-cell receptor (BCR). Protein kinase C (PKC ) is an essential signaling element of the BCR and was recently shown to be overexpressed in human CLL. We used the TCL1 transgenic mouse model to directly target PKC in the development of murine CLL. TCL1 overexpression did restore the CD5 ...

The immunologic surface markers on guished from benign lymphocytosis by surlymphocytes and clinical characteristics of face marker criteria. In untreated CLL, sur35 patients with established ( stages 0-4) face marker characteristics are stable with CLL with absolute lymphocyte counts time and predominantly reflect expansion > 1 5,000/cu mm were compared to those of clones expressing only B cell...

The diagnosis of chronic lymphocytic leukemia (CLL) presenting with ascites is predominantly based on the morphological and immunophenotypic characteristics, which are comparable to peripheral blood and bone marrow cells. However, it is relatively difficult to diagnose CLL due to the pleomorphism of the lymphocytes in ascites. The current study presents an 80-year-old male with a prior diagnosi...

Clonal evolution occurs during the course of chronic lymphocytic leukemia (CLL) and activation-induced deaminase (AID) could influence this process. However, this possibility has been questioned in CLL because the number of circulating AID mRNA(+) cells is exceedingly low; synthesis of AID protein by blood CLL cells has not been demonstrated; the full range of AID functions is lacking in unmuta...